ArticleCNS drugs2022
Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Article in CNS drugs, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- State of the art: Pregnancy in spinal muscular atrophy in the treatment era.Journal of neuromuscular diseases · 2026Review
- Toward adaptive therapeutic timing: integration of mechanistic pharmacology and artificial intelligence in precision dosing.Frontiers in pharmacology · 2026Review
- Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence.The Journal of international medical research · 2025Review
- Successful pregnancy of an SMA type 3 sitter on Nusinersen therapy - a case report.BMC neurology · 2025Article
- l-Type amino acid transporter 1-targeting nanoparticles for antisense oligonucleotide delivery to the CNS.Molecular therapy. Nucleic acids · 2024Article
- Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy.Arquivos de neuro-psiquiatria · 2024Article
- Effects of the COVID-19 Pandemic on SMA Screening and Care: Physician and Community Insights.Neurology and therapy · 2023Article
- Examining Real-World Adherence to Nusinersen for the Treatment of Spinal Muscular Atrophy Using Two Large US Data Sources.Advances in therapy · 2023Article
- Adherence and Persistence to Nusinersen for Spinal Muscular Atrophy: A US Claims-Based Analysis.Advances in therapy · 2023Article
- Role of autophagy and transcriptome regulation in acute brain injury.Experimental neurology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNusinersen is approved for the treatment of spinal muscular atrophy. The most common approved dosing regimen is four intrathecal loading doses of nusinersen 12 mg; the first three are administered at 14-day intervals followed by a fourth dose 30 days later, and then 12-mg maintenance doses are administered every 4 months thereafter. Interruption of nusinersen treatment in the maintenance dosing phase might occur for a number of clinical reasons.
objectiveThe objective of this report is to describe dosing regimens that allow for the most rapid restoration of steady-state concentrations of nusinersen in the cerebrospinal fluid (CSF) following a treatment interruption during maintenance dosing.
methodsPopulation pharmacokinetic models using integrated pharmacokinetic data from ten nusinersen clinical trials that included a broad range of participants with spinal muscular atrophy treated with intrathecal nusinersen were used to investigate different durations of treatment interruptions during maintenance treatment. Potential dosing regimens for re-initiation of nusinersen were evaluated, with the goal of achieving the quickest restoration of steady-state nusinersen CSF concentrations without exceeding maximal CSF exposures observed during the initial loading period.
resultsOur pharmacokinetic modeling indicates the following regimen will lead to optimal restoration of nusinersen CSF levels after treatment interruption: two doses of nusinersen should be administered at 14-day intervals following treatment interruptions of ≥ 8 to < 16 months since the last dose, and three doses of nusinersen at 14-day intervals for treatment interruptions of ≥ 16 to < 40 months since the last maintenance dose, with subsequent maintenance dosing every 4 months in both instances. After treatment interruptions of ≥ 40 months, the full loading regimen will rapidly restore nusinersen CSF levels.
conclusionsProlonged treatment interruptions lead to suboptimal CSF levels of nusinersen. The optimal regimen to restore nusinersen CSF levels depends on the interval since the last maintenance dose was administered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.